The proposed studies are anticipated to yield important new information as to the presence of specific genetic determinants found in Streptococcus mutans, a microbe strongly associated with a severe dental caries in affecting young children called severe early childhood caries or S-ECC. The long-term benefit of such information should lead researchers toward devising both diagnostic and preventive strategies against dental though better understanding its microbial causation. Using a powerful technique of suppressive subtraction DNA hybridization, the first specific aim is to test the hypothesis that strains of S. mutans found in S-ECC children differ in genetic composition compared to strains found in caries-free (CF) children. Unique genetic loci that are specific to S-ECC strains will be identified and characterized. Some of these genetic loci will prove informative as biomarkers for health or disease. Using the power of multiple test analyses derived artificial intelligence programming; biomarkers will be used as the basis for a modeling algorithm capable of classifying strains of S. mutans in one of two categories (S-ECC or CF). The second aim of this study is to survey strains of S. mutans associated with either S-ECC or CF status for known or suspected genetic elements thought to influence the pathogenesis or virulence of S. mutans. The third aim is to survey a larger, racial/ethnical diverse population of S-ECC or CF children for the presence or absence of the biomarkers identified in the first two aims. It is anticipated that this research will yield genetic markers for disease capable of providing clinicians with a diagnostic test that can assess risk for developing S-ECC. 7.